Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migra...Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.展开更多
Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus CO...Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.展开更多
目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉...目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉正性重构的关系。方法按照住院先后顺序选取2022年1月至2023年6月河南科技大学第一附属医院心血管内科收治的老年CHD合并T2DM患者120例,根据重构指数分为正性重构组47例和非正性重构组73例。比较2组临床资料;采用多因素logistic回归分析冠状动脉正性重构的危险因素;采用Spearman相关性分析TyG和AIP与冠状动脉正性重构的相关性;采用ROC曲线分析TyG和AIP对冠状动脉正性重构的预测价值。结果正性重构组吸烟、三酰甘油、糖化血红蛋白、TyG、AIP显著高于非正性重构组,高密度脂蛋白胆固醇、血钙水平显著低于非正性重构组(P<0.05,P<0.01)。单因素logistic回归分析显示,吸烟、三酰甘油、高密度脂蛋白胆固醇、糖化血红蛋白、血钙、TyG、AIP是老年CHD合并T2DM患者冠状动脉正性重构的危险因素(P<0.05,P<0.01)。多因素logistic回归分析显示,TyG(OR=7.253,95%CI:2.458~13.364,P=0.035)、AIP(OR=6.017,95%CI:2.205~12.025,P=0.030)是老年CHD合并T2DM患者冠状动脉正性重构的独立危险因素(P<0.05)。TyG、AIP预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积分别为0.783、0.766,联合预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积为0.868,显著优于单独预测(P<0.05)。结论TyG和AIP与老年CHD合并T2DM患者冠状动脉正性重构密切相关,可作为预测冠状动脉正性重构的有效指标,对临床早期识别高危患者及制定个体化干预策略具有重要意义。展开更多
目的了解中老年2型糖尿病(type 2 diabetes mellitus,T2DM)患者少肌性肥胖(sarcopenic obesity,SO)患病率及不同诊断方法之间的一致性。方法采用系统随机抽样法选取2016年1月至2018年3月于北京地区9家医院内分泌科就诊的≥50岁T2DM患者...目的了解中老年2型糖尿病(type 2 diabetes mellitus,T2DM)患者少肌性肥胖(sarcopenic obesity,SO)患病率及不同诊断方法之间的一致性。方法采用系统随机抽样法选取2016年1月至2018年3月于北京地区9家医院内分泌科就诊的≥50岁T2DM患者,使用生物阻抗法进行身体成分检测;根据2022年欧洲临床营养与代谢学会(European Society for Clinical Nutrition and Metabolism,ESPEN)和欧洲肥胖研究协会(European Association for the Study of Obesity,EASO)方法定义SO,另外3种方法通过肌少症和肥胖的组合进行诊断。肌少症使用2019年亚洲肌少症工作组(Asian Working Group for Sarcopenia,AWGS)建立的标准来定义,肥胖通过体脂(percent of body fat,PBF)、腰围(waist circumference,WC)和体质量指数(body mass index,BMI)来定义。卡方检验进行率的比较,Cohens kappa统计分析比较4种方法的诊断一致性。结果共纳入1125例T2DM受试者,男性586例,年龄[61.2(55.3,67.4)]岁;女性539例,年龄[62.0(56.3,68.1)岁]。使用ESPEN/EASO共识、AWGS+PBF、AWGS+WC和AWGS+BMI标准,中老年T2DM患者SO患病率分别为41.6%、20.4%、30.1%和18.8%。4种方法之间的诊断一致性存在异质性(κ:0.109~0.655)。ESPEN/EASO共识与AWGS+PBF诊断一致性良好(κ:0.655),AWGS+体脂与AWGS+BMI诊断一致性良好(κ:0.637),AWGS+WC与AWGS+BMI(κ:0.359)、与AWGS+PBF诊断一致性中等(κ:0.330)。结论中老年T2DM患者SO患病率高,患病率和诊断一致性在不同诊断方法中存在差异,ESPEN/EASO的共识诊断率最高,AWGS+BMI诊断率最低,ESPEN/EASO共识与AWGS+体脂具有良好的诊断一致性。展开更多
文摘Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.
文摘Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.
文摘目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉正性重构的关系。方法按照住院先后顺序选取2022年1月至2023年6月河南科技大学第一附属医院心血管内科收治的老年CHD合并T2DM患者120例,根据重构指数分为正性重构组47例和非正性重构组73例。比较2组临床资料;采用多因素logistic回归分析冠状动脉正性重构的危险因素;采用Spearman相关性分析TyG和AIP与冠状动脉正性重构的相关性;采用ROC曲线分析TyG和AIP对冠状动脉正性重构的预测价值。结果正性重构组吸烟、三酰甘油、糖化血红蛋白、TyG、AIP显著高于非正性重构组,高密度脂蛋白胆固醇、血钙水平显著低于非正性重构组(P<0.05,P<0.01)。单因素logistic回归分析显示,吸烟、三酰甘油、高密度脂蛋白胆固醇、糖化血红蛋白、血钙、TyG、AIP是老年CHD合并T2DM患者冠状动脉正性重构的危险因素(P<0.05,P<0.01)。多因素logistic回归分析显示,TyG(OR=7.253,95%CI:2.458~13.364,P=0.035)、AIP(OR=6.017,95%CI:2.205~12.025,P=0.030)是老年CHD合并T2DM患者冠状动脉正性重构的独立危险因素(P<0.05)。TyG、AIP预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积分别为0.783、0.766,联合预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积为0.868,显著优于单独预测(P<0.05)。结论TyG和AIP与老年CHD合并T2DM患者冠状动脉正性重构密切相关,可作为预测冠状动脉正性重构的有效指标,对临床早期识别高危患者及制定个体化干预策略具有重要意义。
文摘目的了解中老年2型糖尿病(type 2 diabetes mellitus,T2DM)患者少肌性肥胖(sarcopenic obesity,SO)患病率及不同诊断方法之间的一致性。方法采用系统随机抽样法选取2016年1月至2018年3月于北京地区9家医院内分泌科就诊的≥50岁T2DM患者,使用生物阻抗法进行身体成分检测;根据2022年欧洲临床营养与代谢学会(European Society for Clinical Nutrition and Metabolism,ESPEN)和欧洲肥胖研究协会(European Association for the Study of Obesity,EASO)方法定义SO,另外3种方法通过肌少症和肥胖的组合进行诊断。肌少症使用2019年亚洲肌少症工作组(Asian Working Group for Sarcopenia,AWGS)建立的标准来定义,肥胖通过体脂(percent of body fat,PBF)、腰围(waist circumference,WC)和体质量指数(body mass index,BMI)来定义。卡方检验进行率的比较,Cohens kappa统计分析比较4种方法的诊断一致性。结果共纳入1125例T2DM受试者,男性586例,年龄[61.2(55.3,67.4)]岁;女性539例,年龄[62.0(56.3,68.1)岁]。使用ESPEN/EASO共识、AWGS+PBF、AWGS+WC和AWGS+BMI标准,中老年T2DM患者SO患病率分别为41.6%、20.4%、30.1%和18.8%。4种方法之间的诊断一致性存在异质性(κ:0.109~0.655)。ESPEN/EASO共识与AWGS+PBF诊断一致性良好(κ:0.655),AWGS+体脂与AWGS+BMI诊断一致性良好(κ:0.637),AWGS+WC与AWGS+BMI(κ:0.359)、与AWGS+PBF诊断一致性中等(κ:0.330)。结论中老年T2DM患者SO患病率高,患病率和诊断一致性在不同诊断方法中存在差异,ESPEN/EASO的共识诊断率最高,AWGS+BMI诊断率最低,ESPEN/EASO共识与AWGS+体脂具有良好的诊断一致性。
